Autoimmune diseases comprise many of the most devastating and intractable ailments today, where representative autoimmune diseases include diabetes mellitus, uveoretinitis and multiple sclerosis, among others.
The potential for Tregs to actively regulate autoimmunity and induce long term tolerance has great potential application as a strategy for inducing long-lived tolerance. Taking advantage of Tregs has been complicated by an inability to expand and characterize this minor T cell subset, a population of cells reduced even further in autoimmune-prone animals and patients. For instance, recent studies have suggested that it may be impossible to reverse ongoing autoimmune diabetes due to the autoreactive T cells becoming resistant to suppression during the active phase of the disease. Prior efforts to expand Tregs ex vivo have not achieved clinically sufficient expansion, nor demonstrable in vivo efficacy (e.g. Fu et al., 2004, Am J Transplant. 4, 65-78). The low number of CD4+CD25+ regulatory T cells (Tregs), their anergic phenotype and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection.
A number of US Patent documents relate to T cell expansion, including Horwitz (e.g. U.S. Pat. Nos. 6,803,036 and 6,797,267, and related patent publications); U.S. Pat. No. 6,534,055; US2003/124122A1; US2003/0082806A1; US2002/0058019A1; US2002/0119568A1; US2003/0119185A1; and US2002/0019048A1.